等臂双着丝粒Ph染色体在慢性粒细胞白血病急淋变中的遗传学分析

Analysis of isodicentric Ph chromosomes in chronic myeloid leukemia blast crisis

目的研究等臂双着丝粒Ph染色体在慢性粒细胞白血病急淋变（1ymphoid blast crisis of chronic myeloid leukemia，CML-BLC）中的遗传学及临床特征。方法对2例CML—BLC患者采用24h骨髓培养法制备染色体标本，R显带核型分析，单核苷酸多态性分析（single nucleotide polymorphism，SNP）基因拷贝数变化。用荧光原位杂交（florescence in situ hybridization，FISH）技术验证SNP结果。用多重连接依赖探针扩增（multiplex ligation-dependent probe amplication，MLPA）检测急性淋巴细胞白血病相关基因如CDKN2A／2B和PAX5等的缺失或扩增。结果SNP证实例1的衍生9号有缺失及扩增，与FISH结果相符合。例1和例2的FISH分析可见BCR／ABL融合信号在等臂Ph染色体上，距离远近不同，排列方式为脚对脚（例2）和头对头（例1）。结论CML—BLC中等臂双Ph染色体预示对格列卫治疗抵抗，而用达沙替尼治疗有效。

Objective To explore the genetic and clinical characteristics of isodieentric Ph chromosomes [idic（Ph）] in lymphoid blast crisis of chronic myeloid leukemia （CML-BLC）. Methods Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations （CNV） were analyzed by single nueleotide polymorphism array （SNP array） in case 1. The results were confirmed with fluorescence in situ hybridization （FISH）. Variations of acute lymphoblastic leukemia-related genes including CDKN2A/AB and PAX5 were detected by multiplex ligation-dependent probe amplication （MLPA）. Results Deletions and duplications on derivative chromosome 9 detected by FISH were confirmed by SNP array analysis. The distances between the BCR/ ABL fusion signals on the idic（Ph） chromosomes in the two patients have differed greatly. The idic（Ph） in the second patient was supposed to be formed by two Ph chromosomes joined at their q terminals, where as the idic（Ph） in the first patient have been shown to be fused at the satellite regions of their p arms. Conclusion The idic（Ph） chromosomes presented in CML-BLC may predict resistance to Imatinib and response to Dasatinib.